NeoBlade for NCRI Meeting

Nick James
University of Warwick
@Prof_Nick_James
#NJBladderCancer
1

Background
Bladder cancer outcomes have not
significantly improved for 30 years
Zehnder P, Studer UE, Skinner EC, Thalmann GN, Miranda G, Roth B, Cai J,
Birkhauser FD, Mitra AP, Burkhard FC, Dorin RP, Daneshmand S, Skinner
DG, Gill IS. Unaltered oncological outcomes of radical cystectomy with
extended lymphadenectomy over three decades. BJU Int 2013;112:E51-8

Presented by: Nick James

Bladder cancer is a systemic

disease
No plateau in
survival curves
Local control
Surgery or RT

Metastases
Systemic
therapy
Patel et al, GU ASCO 2014,
Data from 14,697 UK cystectomies 2002-2012

Neoadjuvant chemotherapy
US Intergroup Trial

Surgery +/- MVAC chemotherapy

BA06 EORTC 30894

Surgery or RT +/- CMV chemotherapy

Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally
advanced bladder cancer. New England Journal of Medicine 2003;349:859-66.
Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and
vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol 2011;29:2171-7.

MRC/EORTC Trial - Loco-regional and

metastatic control

Locoregional control

Metastatic control

Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. International phase III trial assessing
neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder
cancer: long-term results of the BA06 30894 trial. J Clin Oncol 2011;29:2171-7.

NEO-BLADE
Phase II randomised placebo controlled
Neoadjuvant chemotherapy study of Nintedanib
with Gemcitabine and Cisplatin in locally advanced
muscle invasive bladder cancer
PI Syed Hussain
Local PI and TMG member N James

Background
Neoadjuvant chemotherapy is part of
standard care and improves OS
Nintedanib is triple angiogenesis inhibitor
VEGFR, PDGFR, FGFR

Complements TUXEDO trial of chemoRT

NCRI badged, commercially supported

Trial Design and Summary

Eligible patient

Randomise

Gem/Cis 12 weeks
7.5mg/kg IV every 3 weeks for 51
weeks (max. 17 infusions over 1
year, or until disease progression)

Gem/Cis 12 weeks
+ Nintedanib 200mg bd for 12
weeks

Radical therapy as per clinician choice

Primary outcomes:
Pathological complete response
Secondary outcomes:
Progression free survival (defined as the date of randomisation to date of confirmed progression or death from any
cause)
Overall survival (defined as the date of randomisation to date of death from any cause)
Toxicity

Resource Requirements
1. CT Abdo, Chest and Pelvis is required at baseline within 8
weeks of randomisation and after cycle 3. This is standard of
care
2. No radionuclide administrations are required for this trial and so
an ARSAC application will no be required
3. Chemotherapy is standard of care
4. Additional pharmacy requirements for Nintedanib/placebo
5. Data management requirement is set at 2 hours per week.
6. Blood tests are as per standard of care apart from coagulation
at baseline and optional samples for linked translational studies
7. ECG is extra
8. No further additional tests
9. Recruitment is 2 years, sample size 120 pts across 6 UK sites
hence target is 20 pts over 2 years.

Conclusions
Neoadjuvant chemotherapy improves overall
survival
Trials in neoadjuvant setting give early readout on efficacy of drugs